This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have recently identified and functionally characterized the human SLX1 and SLX4 proteins. Both proteins appear to be required in response to MMS treatment while only SLX4 is required for survival following exposure to DNA inter-strand crosslinking agents. SLX1 is a 5'flap endonuclease which is strongly stimulated by its association with SLX4. Furthermore, the SLX1-SLX4 complex displays a robust Holliday junction resolvase activity suggesting that it is involved in homologous recombination events. Importantly, we have shown that SLX4 also interacts with the XPF and MUS81 subunits of the XPF-ERCC1 and MUS81-EME1 DNA repair/recombination endonucleases and have proposed that SLX4 may act as a docking platform for multiple structure-specific endonucleases.